國家衛生研究院 NHRI:Item 3990099045/11719
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    题名: Trans-ethnic fine mapping of previously identified QT interval loci in han Chinese discover ethnic-specific signals associated with inflammation pathway
    作者: Juang, JM;Chen, YH;Chien, LH;Wu, IC;Hsu, CC;Chen, LN;Tang, FC;Wang, CC;Juan, CC;Chiu, HC;Lo, HM;Hwang, JJ;Chang, IS;Lin, JL;Hsiung, C
    贡献者: Institute of Population Health Sciences;National Institute of Cancer Research
    摘要: Introduction: Prolongation of QT interval (QT) predisposes to sudden cardiac death. Genome-wide association study (GWAS) studies of QT primarily performed in European-ancestry (EA) populations discovered several QT related loci. It is unclear whether these loci can be generalized to other ethnic groups, such as Han Chinese (HC) population. Furthermore, the association of QT related variants and clinical outcomes were not investigated before. Purpose: We aimed to identify novel and population-specific QT related loci and variants in Han Chinese population, as well as the association between QT related variants and clinical outcomes. Methods: We conducted densely fine mapping on the 18 QT GWAS loci identified in EA studies by the customized Metabochip in 2,517 unrelated HC individuals, and independently performed replication study in 2,013 ethnically-matched individuals from TAICHI consortium. Results: Using Metabochip-genome wide analyses and replication study, we identified 10 variants in 6 known loci significantly associated with QT that collectively explain 3.47% of QT variation. Among them, 3 were novel (Han Chinese-specific) variants (rs41312532 in KCNH2, P=4.7E-07; rs4817659, P=4.6E-11 and rs2070359, P=4.4E-08 in KCNE1) and1 (rs12143842 in NOS1AP, P=2.3E-16) were reported in EA and African American (Table 1). Furthermore, we found that a larger number of the identified QT variants predicts a longer QT interval (averagely +2.53ms/risk allele, P<2E-16). Protein-Protein interaction network analysis of gene products in the identified variants suggested that two highlyinteracting proteins (INFAR1 and INFGR2) were associated withinflammation (P<0.01). Thereafter, we found that the serum C-reactive protein (CRP) level was positively correlated with the number of the QT variants after adjusted age, gender and body mass index (P=0.009). Of 98 known QT variants, 36 variants including rs13017846 in SLC8A1 were significantly replicated in HC population by imputation analysis. Conclusion: These results demonstrated that the same loci affects QT across multiple populations and novel variants exist in HC population. Our integration of common variant associations, protein-protein interaction screens and QT-CRP association provides new insights into cardiac electrophysiology.
    日期: 2017-08
    關聯: European Heart Journal. 2017 Aug;38(Suppl. 1):259.
    Link to: https://doi.org/10.1093/eurheartj/ehx502.P1339
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0195-668X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000440509301045
    显示于类别:[許志成] 會議論文/會議摘要
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